The main story of my PhD research project is finally out in @JCellBiol today! https://t.co/ZgGgFW1ksJ We were looking at how Vaccinia virus circumvents host immunity by disabling the autophagy machinery through depletion of sequestome-like receptors (SLRs). For a 🧵see below:

#Curious2024 was an amazing conference! Many thanks for accepting my abstract and waiving the conference fee @FutureInsight. It has been a great pleasure to hear so many distinguished scientists speak on their work!

I've seen a lot of PhD students around me getting very stressed lately about not producing results, worrying they will never pass or publish. So I went through my PhD paper and labelled what I produced when. Conclusion: I could have been on the beach for all of year 2 😉

Vaccinia virus subverts xenophagy through phosphorylation and nuclear targeting of p62, say Melanie Krause @m_krause0206, Jason Mercer @MercerLab and colleagues @ucl @UoBbiosciences: https://t.co/fXOrnvz4nC @SamolejJ @ayakimovich @kvjanos @MoonaHuttunen @SamuelLaraR @FrickelLab

.@m_krause0206 @MercerLab et al. @ucl @UoBbiosciences show that cytosolic replicating poxviruses disarm xenophagy during early infection by targeting a subset of #autophagy receptors required for pathogen detection https://t.co/1vjEh2o1An #Virology

9/9 And lastly thank you to all of our colleagues who kindly shared viruses and reagents with us, especially @mattw_unl @TerjeJohansen17 and @LabYoule !

8/9 Thank you to all co-authors who helped putting this story together! Especially @SamolejJ for endless repeats of fractionation western blots for the revision😉, but also @ayakimovich @kvjanos @MoonaHuttunen @SamuelLaraR @FrickelLab and @MercerLab

7/9 Direct action of VACV on p62 pointed towards the viral kinases B1 and F10. Depletion of either did not abolish the phenotype. Only absence of both proteins re-established cytoplasmic p62, suggesting high importance of nucleoplasmic shuttling of p62 for VACV replication.

6/9 Depletion of the 2nd NLS abrogates the nuclear phenotype. p62 now co-localizes with VACV replication sites, presumably facilitating its degradation which is indicated by lower viral yields.

5/9 Drug inhibition of early, intermediate and late genes pointed to a set of early VACV genes. Looking at the phosphorylation status of p62, we observed an increase in phosphorylation levels at its 2nd NLS. We confirmed that the phosphorylation is caused directly by VACV.

4/9 The third SLR sequestome1 or p62 however is not degraded, but shunted into the nucleus during the course of infection from 2hpi up until 18hpi.

3/9 Looking at all 5 known SLRs we realized that over-expression of three of these restricts VACV infection. Out of the three NDP52 and Tax1Bp1 are degraded during the course of infection.

2/9 Autophagy receptors (SLRs) link ubiquitinated cytoplasmic content such as proteins and virus particles into forming autophagosomes by binding to ubiquitin and LC3 which is present on the phagophore membrane.

1/9 VACV is one of very few viruses to exclusively replicate in the host cytoplasm. Most pathogens mainly reside in other sub-cellular compartments due to the potency of autophagy as innate immune defense barrier.

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Once again it has been a great experience to attend and help with organising a @GlobalBRev event! The #Excellerator2023 was packed with amazing panels & keynotes from great speakers. Thank you to all participants & especially the lead organising team & my fellow comms ppl😉!

I'm very happy to share my work using image enabled cell sorting of Cas12a generated cell pools this afternoon at #cshlcrispr23 ! Come by poster 127 if you are interested 😉

When the lovely people at your favourite core facility REALLY want to make sure you understand that the fancy FACS is out of order...😉

If you agree that ERC should remove their academic age limits on ERC grants - please Sign this Petition! Please also RT: #EDI #science #EuropeanScience #ERCgrant https://t.co/ydFU97qdju via @UKChange

Our Stanford site is hiring! If you are interested, feel free to reach out! 😉